Diabetes is a major health care problem, and new therapies are urgently needed. The therapies of interest here - encapsulated pancreatic islets, stem cell constructs and implantable glucose sensors - have a common feature: they all must rely on a supply of glucose, oxygen and other metabolites from the tissues in which they are implanted for continued function. The implantable glucose sensor we have developed can be adapted to serve as a unique test platform for study of the foreign body response to candidate materials to be used in the implants. The outer sensor membrane can be made of a candidate biopolymer and various control materials. Several of these test units will be implanted in a pig test subject for three to six months and glucose and oxygen challenges will be performed weekly to assess tissue permeability. At the end of the implant period, tissue samples will be collected for extensive histologic analysis. Quantitative information from the analysis will be used to reconstruct a specific tissue feature model associated with each sensor. A detailed mass transfer model incorporating the tissue features will be developed to predict glucose and oxygen fluxes, and the predictions will be validated by comparison to the specific substrate flux measurements. The results will be cast as a dynamic model of development of the foreign body response and the associated substrate fluxes for candidate materials and tissue types. The study will provide quantitative and definitive information for design of metabolically active islet devices, stem cell implants and implantable sensors. Implantable pancreatic islet devices, stem cells and glucose sensors have been proposed as therapies for diabetes. For sustained function, each of these devices must be supplied with glucose, oxygen and nutrients from the tissues in which they are implanted. This project will examine the permeability of tissues surrounding implanted devices to assess substrate supply to the implant. This information may accelerate implementation of these therapies. [unreadable] [unreadable] [unreadable]